Asthma is a typical respiratory disease having repetitive and spasmodically symptoms of difficulty in breathing, coughs and stridor. About 30% pediatric asthma patients start to show the symptoms within one year from birth while about 80% of asthma patients show the symptoms at the age of 4-5. In Korea, the rate of asthma outbreak is about 10%.
The incidence rate of asthma varied to some extent depending on the country, race, age and the like. According to the British report in 1991, about 7% of adults and 13.5% of children are suffering from asthma. In Korea, the number of asthma patients is on the increase due to the drastic change in life styles as well as in environmental conditions such as severe pollution and accumulated stress. The age of developing asthma has been lowered recently due to environmental contamination such as pollution and its symptoms have been prolonged.
Respiratory obstruction as one of characteristics of asthma occurs via 3 steps: i.e., contraction of bronchial smooth muscle, tylosis of pulmonary mucosa, and accumulation of sticky mucus in bronchi and bronchioles. Of them, contraction of bronchial smooth muscle is rather easily recovered.
In the attack of extrinsic (allergic) asthma, it is known that IgE plays a very important role and IgG is also often involved. IgE releases mediators (histamine, SRS-A, ECF-A, NCF, PAF, Kinin, PGs, etc.) which induce a hypersensitivity reaction by activating mast cells. The cause of intrinsic (non-allergic) asthma is still not known but this kind of asthma appears to be mediated by autonomic nerves. In an intrinsic asthma patient, a cholinergic stimulus can directly release mediators such as histamine from mast cells, increase secretion of goblet cells, dilate pulmonary blood vessels, and contract trachea, bronchi, and large bronchioles, thereby causing bronchial spasm and increasing release of mucus.
So far there is no cure for asthma. Although there are many methods and drugs which have been used for the prevention of spasm and complications due to asthma they have not been satisfactory. One of the most effective ways of preventing the attack of asthma may be to find the very factors that are involved in causing asthma. Examples of therapeutic agents that have been used to treat asthma are inhaling bronchodilator drugs, oral or injectable bronchodilator drugs (sympathetic stimulators and theophyllines), steroid preparations (inhaling, oral and injectable form, etc.), leukotriene antagonists (montelukast, pranlukast, zileuton, etc.), anti-allergic drugs (cromolyn disodium, ketotifen, etc.) and the like.
Bronchitis can be either acute or chronic. According to its causes, bronchitis is divided into allergic, infectious, and extrinsic bronchitis, while pathologically it is classified catarrhalis, suppurative, occlusive, ulcerative, and infiltrative bronchitis. The most frequent cause of bronchitis is due to infection with bacteria, viruses, fungi and the like. People who normally not infected with the above pathogens can be infected when their systemic immune system gets weakened. Allergic bronchitis can be a direct allergic reaction due to inhalation of allergens or a partial symptom due to a generalized allergic reaction. Extrinsic bronchitis may occur due to a chemical stimulus such as chlorine and sulfur dioxide gas, or due to a physical stimulus such as dusts. People living in large cities with polluted air can be readily exposed to respiratory infections. In case of acute bronchitis, from the pathological point of view, it is easy to observe rubber, swelling, and xerosis and also mucous or suppurative secretions. In general, asthmas can be recovered without incurring complications. However, if it is progressed into a chronic asthma, it results in swelling, tylosis and atrophy. In a prolonged chronic asthma, it results in fiber proliferation, bronchostenosis or pulmonary emphysema. The most peculiar symptoms of bronchitis are coughs and phlegm. If the cause of bronchitis is due to infection, there often develops fever and chest pain, whereas if it is due to extrinsic factors, there often develops irritations on the mucus of mouth, nose, eye, etc. In therapy, cough is considered as a sort of a bodily defense and thus it is not recommended to intentionally stop coughing. It is essential that a therapy for the cause be conducted along with other measures. In winter, it is desirable to increase room temperature and administer a small amount of codeine, atropine, ephedrine, antihistamine agents, and the like. Use of steroids or theophyllines for treating infections is not satisfactory.
Nasal allergic inflammation often refers to nasal allergy or allergic rhinitis. It entails symptoms of sudden continuous coughs, release of a large amount of clear nasal mucus, stuffy nose, heavy head, release of tears, and the like. When the symptoms are similar but the allergens are not identified it is coryza vasomotoria. For example, the above symptoms may occur when body temperature is temporarily lowered in the morning and they are usually recovered within a few hours, and these symptoms are commonly seen in people in a cold season. This can be sometimes confused with nasal cold but it differs from the cold and often accompanies asthma and hives.
The allergic reaction in allergic rhinitis is an antigen-antibody hypersensitivity reaction, wherein histamine is released from mast cells and cell walls of basophils, and arachidonic acid is released to produce prostaglandins and leukotrienes by cyclooxygenase (COX) and 5-lipooxygenase(5-LO), thereby mediating the initial reaction occurring between 2-90 min after being exposed to an antigen and the post reaction occurring 4-8 hrs thereafter. The initial reaction is proceeded with by a mediating substance while the post reaction is mediated by cell infiltration. Further, allergic and non-allergic rhinitis both serve as risk factors for developing asthma.
In therapies, desensitization is performed when the antigen is clearly identified. Other therapies such as use of drugs, surgeries, physical therapies but they are not considered as a complete cure.
There are various respiratory infections due to such as pyogenic bacteria, special bacteria (Mycobacterium tuberculosis, Corynebacterium diphtheriae, spirochete, etc.) viruses, fungi, and they are also divided into acute and chronic respiratory infections. When nasal cavity, pharynx, and larynx are independently infected the diseases are called by their respective organ names. However, when the above organs are infected as a whole they are called as upper airway infections, and a representing example is upper airway disease. Besides, in the event of infections due to special bacteria or fungi, they are also frequently called as upper airway tuberculosis, upper airway diphtheriae, upper airway candida and the like.
As stated above, respiratory diseases such as asthma, allergic rhinitis, acute and chronic bronchitis differ with respect to their causes and symptoms but they have common characteristics in the following few aspects.
First, they are all inflammatory diseases. These respiratory diseases are caused by allergies, infections, etc., but inflammation plays a crucial role in exacerbation and treatment of the diseases. That is, introduction of leukocytes stimulated by allergies, infections, etc., into a respiratory tract and activation therein and the various cytokines released from leukocytes and inflammatory mediators deteriorate diseases and affect the therapeutic treatment.
Second, contraction and relaxation of the respiratory tract does not perform normally thus making respiration difficult. That is, the respiratory tract is impaired thereby performing an excess reaction (asthma) in response to a normal stimulus or it becomes too narrowed to perform a normal bronchial respiration thus requiring an appropriate treatment.
Third, in major drug therapies, anti-inflammatory agents, agents that inhibit respiratory contraction, bronchodilators, agents that inhibit respiratory release play important roles and other therapeutic drugs are also commonly used in combination. For example, anti-histamine drugs, anti-cholinergic drugs, beta 2 receptor agonist, steroids, leukotriene D4 receptor antagonists, phosphodiesterase 4 inhibitor of theophyllines are commonly used. Nevertheless, bronchodilator drugs such as anti-cholinergic drugs, beta 2 receptor agonist, etc., are not effective in treating inflammation but they simply alleviate the symptoms. Therefore, long-term use of the drugs may cause drug resistance and there is also a risk of exacerbation. Steroids which are known effective in treating inflammation but they have serious side effects and are not suitable for long term use and also shown not effective in treating chronic bronchitis. Therefore, the above two drugs have been prescribed to be combined for administration but the steroids drug has been formulated in an inhalation form rather than as one for oral administration due to its adverse effects thus lowering its compliance due to the difficulty in administration. Therefore, there is a need to develop a novel therapeutic drug which can resolve the above-mentioned limitations in the currently used therapeutic drugs and effectively improve the symptoms. However, as stated above, various leukocytes and various cytokines and inflammatory mediators are involved in respiratory diseases, it is difficult to treat the respiratory diseases with a single ingredient chemical and thus a natural extract having various active ingredients and mechanism may be able to serve as an effective therapeutic drug.
Further, there appear to be many causes for respiratory diseases such as asthma, bronchitis, allergic rhinitis, acute lower respiratory infections (bronchitis, bronchiolitis, etc.), acute upper respiratory infection (tonsillitis, pharyngolaryngitis) but they are treated only for temporary release, and there is usually a problem of recurrence of the diseases after treatments. Therefore, prevention and treatment of respiratory diseases has been raised as one of the most important tasks to fulfill in medical science and the development of a novel therapeutic drug for the fundamental prevention and treatment of respiratory diseases is in urgent need.
Sophorae Radix of the present invention to be used as a crude drug is a shrub with a height of 1-2 m. It has about 2-5 cylindrical roots with yellowish brown color. Its stem has a cylindrical shape, has a groove on the surface and is densely covered with short and soft hairs where the upper part of the stem is normally bent in the form of “”, a Chinese letter. Its roots, which are used as drugs after drying, have a long cylindrical shape and are a bit bent with a length of 10-25-35 cm, a diameter of 0.3-1 cm. Its surface is brown or dark brown, has vertically-formed wrinkles and lengthy lenticels with a bit of rotation. Its main place of product is Gwangseo Province in China. In oriental medicines, it has been used to treat tumors, edema, pains, jaundice, diarrhea, hemorrhoid, and the like. Its active ingredients are alkaloids such as matrine, oxymatrine, anagyrine, methylcytisine and the like and flavonoids such as sophoranone, sophoradin, sophoranochromene, sophoradochromene and the like (Chinese Medicine Encyclopedia, Jungdam Publishing, pp. 2627-2632, 1998). However, the effect of Sophorae Radix extract on respiratory diseases has not been studied yet.